Anyone know if it's possible, safe and worthwhile to rent a car in Valparaiso and drive north to La Serena (and back, of course)?
How long will it take?
In my guidebook there's only a brief mention of the route up there, with the observatories La Silla and Mamalluca (the latter being open to public). I'd love to see/visit those. Also, is it possible to visit the Nacional Parque Fray Jorge, and is it worth a visit?
Is there anything else of interest along the way?
We're in Valparaiso in October, btw.

You have to get a license in La Serena to visit the observatories.
A good, scenic road is from La Serena to Agua Negra pass (same road to Cerro Tololo observatory), the pass is open only Jan-Feb, but if it is closed you can go up to the Carabineros check point.
I don´t remember how long it takes from Valparaiso to La Serena, but the roads are good and safe, it will not take long. I liked Los Vilos.

I think that you can get to la Serena in about 7 or 8 hours by car. I don't know about any intriguing spots on the way.
I know that there is one observatory which is open to tourists and you don't need a license or appointment to get a tour. I'm sorry, I don't remember the name of it, but if you go to the plaza in Vicuña you can ask in the tourist office there. If you don't have your own vehicle, they pick people up in minivans and head out at about 8 or 9 p.m.
Have a good trip!

with a car you can reach Serena in 6 hours, the highway is safe and in good shape
about Fray Jorge forest, it is an ecological curiosity, at the hills bordering the sea, grows a southern forest similar you can see in Lake District (south of Chile), this because the slopes of the hills catch the morning fog (camanchaca), all this in a desertic area
info Fray Jorge
about the observatories, there are two clases, the huge scientific and the educational. all are open to the public, but the scientific ask for a previous (at less two month) reservation, in Serena area you can find four huge observatories, at Elqui Valley (worth of a visit) El Tololo and Pachon and north La Serena, La Silla and Las Campanas
try for reservations to La Silla
visitors to La Silla
and for Tololo
visitors to El Tololo
about the educational observatories
Mamalluca observatory
Collowara observatory

Hi Sisbette,
you have lots of info about what to do once you get to La Serena, and lots of good links from Fernando, so I'll address the "possible, safe and worthwhile" part of the question...
possible: sure, lots of car rental agencies in Chile, I've used http://www.gochile.cl/Car/CarRent.asp to find them.
safe: the motorways are fine, I assume the sensible way is to drive to Santiago (2hrs or so) and then on to La Serena (it's a while since I did it, it's almost 500km and with a 120kmh speed limit it's not going to be much under 5hrs. Your main challenge will be in Santiago, where signposts are few and far between. If you haven't had a lot of experience driving in Chile I would avoid rush hour and Friday evening and Monday morning altogether.
worthwhile: Car rental in Chile is relatively expensive. Unless you want to stop on the way (I also liked Los Vilos) I would be inclined to take a bus (lots of choice, I've used Turbus and was happy) and rent a car once I arrived in La Serena.
I've seen the original Valdivian forests, but not the northern cousin at Fray Jorge yet. It looks like it's quite a way off the motorway.
Hope this helps...

Hi Sisbette:
I am chilean and used to live in Viña del Mar (5 miles to Valparaiso). I mildly disagree with answer number 5 recommendation to go to Santiago first. If you take the coast road going North from Viña you will see the most spectacular seascapes , after passing Concon and continuing
you wil pass near the bautiful beaches of Maitencillo, Cachagus, Zapallar and Papudo where you meet the main thoroughfare towards La Serena.
All this wbeautiful section will take at most 1.5 hours , instead of about 3.5 hours going through Santiago. So yo will save 2 hours on your trip, that is if you are not compelled to stop many times along the road to see the magnificent scenaries or to eat seafood in any of the multiple restaurants in tha resort area.